Human DUOX protein localization is not exclusive to thyroid tissue; hDUOX1 is prominent in airway epithelial cells and hDUOX2 in the salivary glands and gastrointestinal tract.

[7][8] Investigations into reactive oxygen species (ROS) in biological systems have, until recently, focused on characterization of phagocytic cell processes.

Genetic analyses have implicated NOX/DUOX derived ROS in biological roles and pathological conditions including hypertension (NOX1),[11] innate immunity (NOX2/DUOX),[12] otoconia formation in the inner ear (NOX3),[13] and thyroid hormone biosynthesis (DUOX1/2).

This unstable superoxide, generated at the extracellular surface, may rapidly convert to hydrogen peroxide and be utilized by the N-terminal peroxidase domain to facilitate tyrosine cross-linking.

Mature DUOX enzymes produce H2O2; this activity is regulated by Ca2+ concentration through triggered dissociation of NOXA1 and possibly other as yet unidentified interacting proteins.

Surprisingly, the heme appears to have two covalent links to the C. elegans protein despite the absence of a second conserved carboxyl group in the active site.